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This article introduces the use of Internet-mediated joint construction (JC) to engage second language (L2) writers to participate in virtual classroom activities in an online teaching environment. Affected by the ongoing COVID-19 pandemic, schools and universities in the People's Republic of China were required to rapidly transit to remote teaching. The switch from the traditional classroom-based scenarios to the online environment was challenging for teachers. One of the extreme difficulties is to engage students in virtual-class activities. To address this issue, the authors designed an Internet-mediated JC teaching practice and implemented it on ClassIn, an online teaching platform for one semester. Analysis of students' after-class online surveys and interviews suggested that the Internet-mediated JC practice helped students to build a connected network and thus engaged them in actively interacting with both the teacher and peers in the online environment. Pedagogical implications are discussed to contribute to the teaching practice of L2 online writing instruction.

Abstract Obstructed atomic insulator is recently proposed as an unconventional material, in which electric charge centers localized at sites away from the atoms. A half-filling surface state would emerge at specific interfaces cutting through these charge centers and avoid intersecting any atoms. In this article, we utilized photoemission spectroscopy and density functional theory calculations to study one of the obstructed atomic insulator candidates, NiP2. A floating surface state with large effective mass that is close to the Fermi level and isolated from all bulk states is resolved on the (100) cleavage plane, implying better catalytic activity in this plane than the previously studied surfaces. Density functional theory calculation results elucidate that this floating surface state is originated from the obstructed Wannier charge centers, albeit underwent surface reconstruction. Our findings not only shed lights on the study of obstructed atomic insulators, but also provide possible route for development of new catalysts.

Abstract Objectives To investigate the roles of Ca2+ influx-regulated circular RNAs (circRNAs) in T cells from patients with systemic lupus erythematosus (SLE). Methods The expression profile of circRNAs in Jurkat cells, co-cultured with and without ionomycin, was analyzed by next-generation sequencing and validated using real-time polymerase chain reaction. The identified Ca2+ influx-regulated circRNAs were further examined in T cells from 42 patients with SLE and 23 healthy controls. The biological function of specific circRNA was investigated using transfection and RNA pull-down assay. Results After validation, we confirmed that the expression levels of circ-ERCC4, circ-NFATC2, circ-MYH10, circ-CAMTA1, circ-ASH1L, circ-SOCS7, and circ-ASAP1 were consistently increased in Jurkat cells following Ca2+ influx. The expression levels of circ-CAMTA1, circ-ASH1L, and circ-ASAP1 were significantly lower in T cells from patients with SLE, with even lower levels observed in those with higher disease activity. Interferon (IFN)-α was found to suppress the expression of circ-CAMTA1. Circ-CAMTA1 bound to pyruvate carboxylase and inhibited its biological activity. Overexpression of circ-CAMTA1, but not its linear form, significantly decreased extracellular glucose levels. Furthermore, increased expression of circ-CAMTA1, but not its linear form, decreased miR-181c-5p expression, resulting increased IL-2 secretion. Conclusion Three Ca2+ influx-regulated circ-RNAs—circ-CAMTA1, circ-ASH1L, and circ-ASAP1 —were significantly reduced in T cells from patients with SLE and associated with disease activity. IFN-α suppressed the expression of circ-CAMTA1, which interacted with pyruvate carboxylase, inhibited its activity, affected glucose metabolism, and increased IL-2 secretion. These findings suggest that circ-CAMTA1 regulated by Ca²⁺ influx modulated T cell function in patients with SLE.

Abstract Knee osteoarthritis (KOA) has a high incidence among the elderly, significantly impacting their quality of life and overall health. Medial unicompartmental knee arthroplasty (UKA) is an excellent choice for treating knee single-compartment lesions, and lower limb alignment has a profound impact on medial UKA. To explore the influence of different lower limb alignments on medial UKA. In this study, we selected MR and CT data of healthy adult male knee joints to establish a complete finite element analysis (FEA) model of the knee joint. After validation, we established a finite element model of medial UKA. Subsequently, we created 60 sets of FEA models with different lower limb alignments to analyze the impact of different lower limb alignments on medial UKA. A vertical load of 1000 N was applied to the FEA models with different lower limb alignments. During the process of shifting the Mikulicz line from the midpoint of the knee joint towards the medial side, the lower limb load was primarily concentrated on the medial compartment. The stress values of the lateral meniscus, tibial cartilage, and femoral cartilage gradually decreased. ROI (region of interest) 1 and ROI 2 showed the maximum principal strain changes, while ROI 3 and ROI 4 exhibited less pronounced fluctuations, with the maximum principal strain roughly proportionally increased. During the process of shifting the Mikulicz line towards the lateral side from the midpoint of the knee joint, the stress on the lateral compartment increased observably. ROI 1, ROI 2, ROI 3, and ROI 4 showed decreased maximum principal strains, approximately inversely proportional changes, but the overall reduction was relatively small. Different lower limb alignments have a profound impact on the short- and long-term joint function after UKA. When the Mikulicz line is 10 mm inside the midpoint of the knee joint or slightly outside, there is a relatively lower risk of tibial component fractures, lower stress on the lateral compartment, and lower load on the prosthesis. During medial UKA, measures such as bone resection and prosthesis selection should be taken to ensure that the Mikulicz line is in the ideal position.

Abstract The mechanical interactions among integrated cellular structures in soft tissues dictate the mechanical behaviors and morphogenetic deformations observed in living organisms. However, replicating these multifaceted attributes in synthetic soft materials remains a challenge. In this work, we develop a smart hydrogel system featuring engineered stiff cellular patterns that induce strain-driven heterogeneous subdomains within the hydrogel film. These subdomains arise from the distinct mechanical responses of the pattern and film domains under applied mechanical forces. Unlike previous studies that incorporate reinforced inclusions into soft matrices to tailor material properties, our method manipulates the localization, integration, and interaction of these subdomain building blocks within the soft film. This enables extensive tuning of both local and global behaviors. Notably, we introduce a subdomain-interface mechanism that allows for the concurrent customization and decoupling of mechanical properties and shape transformations within a single material system—an achievement rarely accomplished with current synthetic soft materials. Additionally, our use of in-situ imaging characterizations, including full-field strain mapping via digital imaging correlation and reciprocal-space patterns through fast Fourier transform analysis of real-space pattern domains, provides rapid real-time monitoring tools to uncover the underlying principles governing tailored multiscale heterogeneities and intricate behaviors.

Abstract Background Teachers’ leadership styles have a significant impact on students’ academic performance, physical health and mental health. Authoritarian leadership, as a typical leadership style, is prevalent in the teacher community. The purpose of this study was to examine the mechanisms by which authoritarian leadership impacts students’ well-being. We also examined the mediating role of emotional exhaustion and the moderating role of narcissism. Methods This study is based on conservation of resources theory. We selected a sample of 369 students from a university in Sichuan province, collected data through two time points, and tested the data using SPSS 24.0 and AMOS 22.0. Results It was found that teachers’ authoritarian leadership negatively impacted students’ well-being and that emotional exhaustion mediated the relationship between authoritarian leadership and well-being. Narcissism not only moderated the effect of authoritarian leadership on emotional exhaustion, but also moderated the mediation role of emotional exhaustion. Conclusions Our findings enriched the research on authoritarian leadership and narcissism, and also had important practical implications for future teacher teaching in higher education.

Abstract The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address this gap by subtracting the genetic effects of a GWAS for intraocular pressure from a GWAS for primary open angle glaucoma to reveal the genetic contribution to primary open angle glaucoma via intraocular pressure-independent mechanisms. Seventeen independent genome-wide significant SNPs were associated with the intraocular pressure-independent component of primary open angle glaucoma. Of these, 7 are located outside known normal tension glaucoma loci, 11 are located outside known intraocular pressure loci, and 2 are novel primary open angle glaucoma loci. The intraocular pressure-independent genetic component of primary open angle glaucoma is associated with glaucoma endophenotypes, while the intraocular pressure-dependent component is associated with blood pressure and vascular permeability. A genetic risk score for the intraocular pressure-independent component of primary open angle glaucoma is associated with 26 different retinal micro-vascular features, which contrasts with the genetic risk score for the intraocular pressure-dependent component. Increased understanding of these intraocular pressure-dependent and intraocular pressure-independent components provides insights into the pathogenesis of glaucoma.

Abstract Background Metabolic dysfunction-associated steatohepatitis (MASH) is a growing global health concern with no effective pharmacological treatments. SNP-630, a newly developed synthetic molecule with multiple mechanisms of action, and a mixture of two of its active metabolites (SNP-630-MS) inhibit CYP2E1 expression to prevent reactive oxygen species generation, thereby reducing the accumulation of hepatic triglycerides and lowering chemokine levels. This study investigated the SNP-630’s potential to alleviate the liver injury in MASH and its efficacy in both a mouse model and patients with MASH to identify a drug candidate that targets multiple pathways implicated in MASH. Methods SNP-630 and SNP-630-MS were separately administered to the MASH mouse model. The tolerability, safety, and efficacy of SNP-630-MS were also evaluated in 35 patients with MASH. The primary endpoint of the study was assessment of the changes in serum alanine aminotransferase (ALT) levels from baseline to week 12, while the secondary endpoints included the evaluation of liver inflammation, steatosis, and fibrosis parameters and markers. Results SNP-630 treatment in mice improved inflammation, liver steatosis, and fibrosis compared with that in the MASH control group. Both SNP-630 and SNP-630-MS treatments markedly reduced ALT levels, hepatic triglyceride content, and the expression of inflammatory cytokines monocyte chemoattractant protein 1 and fibrotic collagen (i.e., Col1a1, Col3a1, and Timp1) in mice. In the clinical trial, patients treated with SNP-630-MS exhibited significant improvement in ALT levels at week 12 compared with baseline levels, with no reports of severe adverse events. This improvement in ALT levels surpassed that achieved with most other MASH candidates. SNP-630-MS demonstrated potential antifibrotic effects, as evidenced by a significant decrease in the levels of fibrogenesis-related biomarkers such as CCL4, CCL5, and caspase 3. Subgroup analysis using FibroScan measurements further indicated the efficacy of SNP-630-MS in ameliorating liver fibrosis. Conclusions SNP-630 and SNP-630-MS demonstrated favorable results in mice. SNP-630-MS showed excellent tolerability in mice and patients with MASH. Efficacy analyses indicated that SNP-630-MS improved liver steatosis and injury in patients with MASH, suggesting that SNP-630 and 630-MS are promising therapeutic options for MASH. Larger scale clinical trials remain warranted to assess the efficacy and safety of SNP-630 in MASH. Trial registration: ClinicalTrials.gov NCT03868566. Registered 06 March 2019-Retrospectively registered, https://clinicaltrials.gov/study/NCT03868566

Abstract Source‐to‐sink analysis examines the effects of source areas and basin (sink) dynamics on the generation, transport, composition, distribution and deposition of sediment in modern and ancient sedimentary systems. Detrital zircon, as one of the most stable detrital minerals, its U–Pb geochronology and geochemistry is pivotal for sedimentary provenance analysis and reconstructing palaeogeography. The South China Sea (SCS), as the largest marginal sea in the Southeast Asia, is closely related to the uplift of the Tibetan Plateau and the evolution of Chinese rivers. In this study, we mainly collect published detrital zircon of Cenozoic sediments in the SCS (include Hainan and Taiwan Islands). These detrital zircon were concentrated on Cenozoic multiple episodic rift basins in the northern part of the SCS. A total of 21,760 detrital zircon U–Pb data from 293 samples and 995 detrital zircon Lu‐Hf isotope data from 22 samples were collected in this dataset, with the main study epochs being the Palaeogene and Neogene. Best ages of these grains are range from 4,691 to 10 Ma and more than half of them within age less than 500 Ma. The 176Hf/177Hf ratios of the SCS samples ranging from 0.280509 to 0.28306 and the εHf(t) values from −63.8 to 24.6. The main age group of the SCS Cenozoic sediments were at 130–95 Ma, 175–130 Ma and 265–230 Ma. The detrital zircon U–Pb age and Lu–Hf isotope data contained in this dataset is an important geological record of the sedimentary and tectonic evolution of the SCS and the evolution of rivers such as the ancient Pearl River and the ancient Red River, which can provide a basis and important clues or exploring the source of sediments in the SCS, the dynamical processes of basin evolution, the evolution of the coastal drainage system and the tectonic uplift of the Tibetan Plateau.

Abstract Complications of detrital zircons databases provide a means for statistically analysing a variety of significant geological problems. In this work, we tried to collect a database about the South China Phanerozoic detrital zircon geochronology data. The data statistics of this paper rely on the OneSediment Working Group of The Deep‐time Digital Earth program (DDE). By November 2022, the database contains a total of 699 samples with 55,532 U–Pb ages and 3,770 effective Hf isotope data, from 130 papers. Abundant information including reference title, sample ID, locality, rock type, research institution, GPS coordinates, U–Pb ages, εHf(t) values, etc., have been involved in our database, and all data can be downloaded from DDE Data Publish & Repository website, https://repository.deep‐time.org/. Through the integrated data, we can improve the previous studies and avoid the waste of resources caused by a large number of repeated studies.

Abstract Background The co-occurrence of Lemierre’s syndrome, primarily triggered by Fusobacterium necrophorum following oropharyngeal infection, with diabetic ketoacidosis (DKA) in diabetes mellitus (DM) patients, underscores a rare but life-threatening clinical scenario. Lemierre’s syndrome induced DKA is extremely rare, with only one case report in adult and no case yet reported in elderly. Case Presentation We reported a case of a 69-year-old female who presented with DKA triggered by deep neck space infection (DNSI), leading to rapid clinical deterioration within 6 h that necessitated high flow nasal cannula (HFNC) and antibiotic administration. Laboratory findings included leukocytosis, elevated serum C-reactive protein, hyperglycemia, ketonemia, and severe metabolic acidosis. Culture of the fluid from a neck mass puncture drainage and blood were positive for Klebsiella pneumoniae. The patient was further complicated by thrombosis of the left internal jugular vein with extension to the sigmoid and a neck abscess surrounding the carotid artery sheath, consistent with Lemierre’s syndrome. This condition was managed aggressively with fluid resuscitation, insulin therapy, surgical drainage, antibiotics, and anticoagulation led to a significant improvement in her condition. Following a 13-day hospitalization, there was significant clinical improvement, culminating in the patient’s discharge. Conclusions The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of DKA and Lemierre’s syndrome among clinicians. Early recognition and treatment are crucial to prevent mortality in such complex cases.

Abstract Biocatalysis is an attractive approach for the synthesis of chiral pharmaceuticals and fine chemicals, but assessing and/or improving the enantioselectivity of biocatalyst towards target substrates is often time and resource intensive. Although machine learning has been used to reveal the underlying relationship between protein sequences and biocatalytic enantioselectivity, the establishment of substrate fitness space is usually disregarded by chemists and is still a challenge. Using 240 datasets collected in our previous works, we adopt chemistry and geometry descriptors and build random forest classification models for predicting the enantioselectivity of amidase towards new substrates. We further propose a heuristic strategy based on these models, by which the rational protein engineering can be efficiently performed to synthesize chiral compounds with higher ee values, and the optimized variant results in a 53-fold higher E-value comparing to the wild-type amidase. This data-driven methodology is expected to broaden the application of machine learning in biocatalysis research.

Abstract Racial and ethnic minorities bear a disproportionate burden of type 2 diabetes (T2D) and its complications, with social determinants of health (SDoH) recognized as key drivers of these disparities. Implementing efficient and effective social needs management strategies is crucial. We propose a machine learning analytic pipeline to calculate the individualized polysocial risk score (iPsRS), which can identify T2D patients at high social risk for hospitalization, incorporating explainable AI techniques and algorithmic fairness optimization. We use electronic health records (EHR) data from T2D patients in the University of Florida Health Integrated Data Repository, incorporating both contextual SDoH (e.g., neighborhood deprivation) and person-level SDoH (e.g., housing instability). After fairness optimization across racial and ethnic groups, the iPsRS achieved a C statistic of 0.71 in predicting 1-year hospitalization. Our iPsRS can fairly and accurately screen patients with T2D who are at increased social risk for hospitalization.

Background/purpose: Challenges exist regarding the bonding efficiency of polyaryletherketone (PAEK), a high-performance thermoplastic, attributed to its chemical inertness and hydrophobic surface, hindering effective bonding with resin-matrix cement. This research explored the impact of handheld nonthermal plasma (HNP), under varying operational parameters, on PAEK surface wettability and changes in bonding performance with cement. Materials and methods: Three types of disc-shaped PEAK specimens were prepared, with surface treatments categorized as grinding, airborne-particle abrasion (APB), and HNP. Surface wettability was analyzed using a contact angle analyzer (n = 10). Specimens were bonded with resin cement and subjected to artificial aging tests: distilled water bath (NA), thermocycling, and highly accelerated stress tests (n = 10 for each test). Shear bond strength (SBS) was measured, failure modes were analyzed, and statistical analyses were conducted. Results: The HNP markedly improved PAEK surface wettability, achieving superhydrophilicity (P

Abstract In dairy farming, the uncertainty of cow calving date often imposes waiting costs for days on farmers. Improving the accuracy of calving date prediction would mitigate these costs, specifically before a few days of the event. We monitored and analyzed the heart rate patterns of eight pregnant cows in the days leading up to calving using a dedicated monitoring device. We decomposed the heart rate data into three distinct components: trend, daily cycle, and the remainder, and discovered that the heart rate trend exhibited a sharp decline more than 40 h before the calving event via the trend turning point. To detect the turning point, we applied common financial technical indicators traditionally used to identify turning points of asset prices in trading markets for the extracted heart rate trend. This study remains a feasibility study because of the limited observations, but it indicates that these indicators can effectively capture the trend’s turning point in real time, offering a promising approach for enhanced calving prediction. In addition to discussing the practical implications for cow management, we also contemplate the broader utility of these technical indicators in the context of various dynamic scientific data analyses.

Abstract The charge density wave (CDW), as a hallmark of vanadium-based kagome superconductor AV3Sb5 (A = K, Rb, Cs), has attracted intensive attention. However, the fundamental controversy regarding the underlying mechanism of CDW therein persists. Recently, the vanadium-based bi-layered kagome metal ScV6Sn6, reported to exhibit a long-range charge order below 94 K, has emerged as a promising candidate to further clarify this core issue. Here, employing micro-focusing angle-resolved photoemission spectroscopy (μ-ARPES) and first-principles calculations, we systematically studied the unique CDW order in vanadium-based bi-layered kagome metals by comparing ScV6Sn6 with its isostructural counterpart YV6Sn6, which lacks a CDW ground state. Combining ARPES data and the corresponding joint density of states (DOS), we suggest that the VHS nesting mechanism might be invalid in these materials. Besides, in ScV6Sn6, we identified multiple hybridization energy gaps resulting from CDW-induced band folding, along with an anomalous band dispersion, implying a potential electron-phonon coupling-driven mechanism underlying the formation of the CDW order. Our finding not only comprehensively maps the electronic structure of V-based bi-layer kagome metals but also provides constructive experimental evidence for the unique origin of CDW in this system.

Abstract The host limits Mycobacterium tuberculosis (Mtb) by enriching copper in high concentrations. This research investigates how Mtb escapes copper stress. The membrane protein encoded by Mtb Rv0102, when its homolog in M. smegmatis (MSMEG_4702) was knocked out, resulted in a fourfold decrease in intracellular copper levels and enhanced tolerance to elevated extracellular copper concentrations. Similarly, knockout mutants of its homolog in M. marinum (MMAR_0267) showed increased virulence in zebrafish and higher bacterial load within macrophages. In THP-1 cells infected with MMAR_0267 deletion mutants, the intracellular survival of these mutants increased, along with reduced THP-1 cell apoptosis. Deficiency in copper down-regulated the transcriptional level of the virulence factor CFP-10 in M. marinum, suppressed cytosolic signaling via the macrophage STING pathway, leading to decreased production of IFN-β and reduced cell apoptosis. In conclusion, these findings highlight the significant impact of copper on the survival and reproduction of mycobacteria, underscoring the importance of studying mycobacterial adaptation mechanisms in copper-rich environments.

Objective: To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1 (SIRT1) signaling pathway. Methods: H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay. The protein expressions of SIRT1 and p38 MAPK were measured by Western blot. RT-qPCR was also used to determine S1RT1 mRNA expression. In addition, intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated. Results: Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability. It also increased SIRT1 and decreased p-p38 MAPK protein expressions. In addition, thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress, and enhanced antioxidant enzyme activities. However, silencing S1RT1 abrogated the protective effects of thrombopoietin, as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels. Conclusions: Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway. However, its protective effects need to be further verified in animal tests.

Abstract Background Simulation-Based Learning (SBL) is increasingly adopted in medical education across various specialties, employing realistic simulations to significantly enhance learning experiences. However, a comprehensive evaluation of its effectiveness specifically in endocrinology has not yet been conducted. The study aims to systematically review and meta-analyze the impact of SBL versus Non-Simulation-Based Learning (NSBL) on knowledge acquisition, skills, satisfaction, and interest in learning among endocrinology trainees. Methods This systematic review and meta-analysis adhered to the PRISMA guidelines, searching PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Weipu, and Chinese Biomedical Database (CBM) until March 2024. We included randomized controlled trials comparing SBL to NSBL in endocrinology education. The quality evaluation relied on the Cochrane risk-of-bias assessment tool. The main results included evaluations from both theoretical and practical assessments. Additional measures consisted of assessing satisfaction and interest in learning. Results We identified 22 studies suitable for systematic review and 21 for meta-analysis, involving a total of 2517 participants. SBL greatly enhanced theoretical knowledge [standardized mean difference (SMD) = 1.00, 95% confidence interval (CI): 0.68–1.32, P

Abstract Background This study aims to investigate the causal relationship of human plasma metabolites and metabolic ratios with schizophrenia (SCZ). Methods We employed Mendelian Randomization (MR) approach to comprehensively analyze two large-scale metabolomics and schizophrenia Genome-Wide Association Study (GWAS) datasets, incorporating a total of 1091 metabolites and 309 metabolic ratios, with 52017 schizophrenia patients and 75889 healthy controls. The inverse variance-weighted (IVW) method was utilized to estimate the causal relationship between exposure and outcome. To provide a more comprehensive evaluation, additional Mendelian Randomization (MR) approaches were employed, including MR-Egger regression, weighted median, simple mode, and weighted mode methods. These analyses assessed the causal effects between blood metabolites, metabolic ratios, and schizophrenia. Tests for pleiotropy and heterogeneity were conducted. False Discovery Rate (FDR) correction was applied to account for multiple comparisons and heterogeneity, ensuring the robustness and reliability of our findings. Consistent with previous studies, an FDR threshold of

Abstract Eastern Taiwan overlies a suture zone between the Eurasian Plate and the Philippine Sea Plate and is characterized by frequent earthquakes, often resulting in significant disasters. Notably, the region exhibits characteristics such as a high frequency of earthquakes and a short recurrence period for intense seismic events. While prior research has explored seismic b values across various periods in Taiwan, detailed investigations of the b value in the eastern region are lacking. This study employs the earthquake catalog compiled by the Taiwan Central Weather Administration to analyze spatial–temporal variations in b values in eastern Taiwan. The analysis encompasses seismic events occurring between January 1996 and June 2019. The seismic catalog is divided into three distinct time periods related to large seismic events: period I, 1996–2003 (the Chengkung earthquake); period II, 2003–2013 (the Ruisui earthquake); and period III, 2013–2019 (the Hualien earthquake). Our results indicate that most seismic events with a magnitude greater than 6 are associated with low b values. The overall b value increases during period II and then decreases substantially during period III. Although the estimated b values changed slightly, but the uncertainty in b values remained stable in this study. The epicenters of large earthquakes often overlap with areas with lower b values, especially in plate suture zones, which means that areas with lower b values usually have a higher probability of larger earthquakes. Given the extremely high potential for a catastrophic earthquake, mitigating measures should be adopted at all times. Graphical Abstract

Abstract Microbial fuel cells utilize exoelectrogenic microorganisms to directly convert organic matter into electricity, offering a compelling approach for simultaneous power generation and wastewater treatment. However, conventional microbial fuel cells typically require thick biofilms for sufficient metabolic electron production rate, which inevitably compromises mass and charge transport, posing a fundamental tradeoff that limits the achievable power density (

Abstract KIF18B is a key member of the kinesin-8 family, involved in regulating various physiological processes such as microtubule length, spindle assembly, and chromosome alignment. This article briefly introduces the structure and physiological functions of KIF18B, examines its role in malignant tumors, and the associated carcinogenic signaling pathways such as PI3K/AKT, Wnt/β-catenin, and mTOR pathways. Research indicates that the upregulation of KIF18B enhances tumor malignancy and resistance to radiotherapy and chemotherapy. KIF18B could become a new target for anticancer drugs, offering significant potential for the treatment of malignant tumors and reducing chemotherapy resistance.

Abstract The IL6-GP130-STAT3 pathway facilitates lung cancer progression and resistance to tyrosine kinase inhibitors. Although glycosylation alters the stability of GP130, its effect on the ligand IL6 remains unclear. We herein find that N-glycosylated IL6, especially at Asn73, primarily stimulates JAK-STAT3 signaling and prolongs STAT3 phosphorylation, whereas N-glycosylation-defective IL6 (deNG-IL6) induces shortened STAT3 activation and alters the downstream signaling preference for the SRC-YAP-SOX2 axis. This signaling shift induces epithelial-mesenchymal transition (EMT) and migration in vitro and metastasis in vivo, which are suppressed by targeted inhibitors and shRNAs against SRC, YAP, and SOX2. Osimertinib-resistant lung cancer cells secrete a large amount of deNG-IL6 through reduced N-glycosyltransferase gene expression, leading to clear SRC-YAP activation. deNG-IL6 contributes to drug resistance, as confirmed by in silico analysis of cellular and clinical transcriptomes and signal expression in patient specimens. Therefore, the N-glycosylation status of IL6 not only affects cell behaviors but also shows promise in monitoring the dynamics of lung cancer evolution.

Abstract Objective This study aimed to evaluate the impact of adding 4 mg estradiol valerate to progesterone for luteal support on pregnancy rates in IVF cycles following a long protocol with reduced luteal serum estradiol levels post-hCG triggering. Design, setting, and participants The prospective randomized controlled trial was conducted at a public tertiary hospital reproductive center with 241 patients who experienced a significant decrease in serum estrogen levels post-oocyte retrieval. Interventions Participants received either a daily 4 mg dose of estradiol valerate in addition to standard progesterone or standard progesterone alone for luteal support. Results The ongoing pregnancy rate did not show a significant difference between the E2 group and the control group (56.6% vs. 52.2%, with an absolute rate difference (RD) of 4.4%, 95% CI -0.087 to 0.179, P = 0.262). Similarly, the live birth rate, implantation rate, clinical pregnancy rate, early abortion rate, and severe OHSS rate were comparable between the two groups. Notably, the E2 group had no biochemical miscarriages, contrasting significantly with the control group (0.0% vs. 10.7%, RD -10.7%, 95% CI -0.178 to -0.041, P = 0.000). In the blastocyst stage category, the clinical pregnancy rate was notably higher in the E2 group compared to the control group (75.6% vs. 60.8%, RD 14.9%, 95% CI 0.012 to 0.294, P = 0.016). Conclusion Adding 4 mg estradiol valerate to progesterone for luteal support does not affect the ongoing pregnancy rate in embryo transfer cycles using a long protocol with a significant decrease in serum estradiol levels after hCG triggering. However, it may reduce biochemical miscarriages and positively impact clinical pregnancy rates in blastocyst embryo transfer cycles. Trial registration ChiCTR1800020342.

Abstract Background The study assessed the association between COVID-19 and new-onset obstructive airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis among vaccinated individuals recovering from COVID-19 during the Omicron wave. Methods This multicenter retrospective cohort study comprised 549,606 individuals from the U.S. Collaborative Network of TriNetX database, from January 8, 2022, to January 17, 2024. The hazard of new-onset obstructive airway diseases between COVID-19 and no-COVID-19 groups were compared following propensity score matching using the Kaplan–Meier method and Cox proportional hazards model. Results After propensity score matching, each group contained 274,803 participants. Patients with COVID-19 exhibited a higher risk of developing new-onset asthma than that of individuals without COVID-19 (adjusted hazard ratio (aHR), 1.27; 95% CI, 1.22–1.33; p

Background: The association between Chinese herbal medicine (CHM) and the risk of developing major adverse cardiovascular events (MACEs) in patients with dialysis hypotension is unclear and has not yet been investigated. This study aimed to determine whether CMH intervention could reduce the risk of MACEs in patients with dialysis hypotension. Methods: The study data from the Taiwan National Health Insurance Research Database were analyzed to clarify this association. For this study, a case-control design with a cohort of patients who received hemodialysis (HD) from 2008 to 2018, 20 295 HD patients who had received blood pressure (BP) raising drugs were identified. After 1:1 frequency-matching, 730 patients were identified as CHM users and CHM non-users. Vascular access revision/reconstruction and MACEs were observed as the main outcomes during the follow-up period. Results: The occurrence of vascular access revision/reconstruction in HD patients receiving BP raising drugs was associated with a 0.34-fold lower risk in CHM users than in CHM non-users [adjusted hazard ratio (aHR) = 0.34, 95% confidence interval (CI) = 0.26, 0.45]. The occurrences of MACEs in HD patients receiving BP raising drugs was associated with a 0.41-fold lower risk in CHM users than in CHM non-users (aHR = 0.41, 95% CI = 0.33, 0.51). A markedly predominant effect was observed in those receiving CHM for more than 180 days (aHR = 0.32; 95% CI = 0.22, 0.45). Conclusion: The findings revealed lower vascular access dysfunction and MACEs risk correlated with the use of CHM treatment among HD patients who received BP raising drugs.

Multidimensional theory of mind assessments should include items assessing both explicit theory of mind (theory of mind knowledge) and applied theory of mind (application of theory of mind knowledge in real-life contexts). However, the two theory of mind scores cannot be interpreted collectively to identify children having mismatched explicit and applied theory of mind due to the lack of links between the two scores. To map the information between two theory of mind scores, data of 221 autistic children aged 3-12 years were extracted. Items of the Theory of Mind Task Battery and Theory of Mind Inventory-2 were used to respectively assess the explicit and applied theory of mind. Rasch analysis and correlation coefficients were used to examine the model fits/dimensionality and relationships. After the removal of misfit items, the remaining 45 items showed satisfactory model fits (infit and outfit mean squares < 1.35). Large correlation (r = 0.63) was found between the Rasch scores of the two theory of mind constructs. The scatter plots highlighted that each applied theory of mind score could reflect multiple explicit ToM scores. Accordingly, the information from each theory of mind measure is unique and irreplaceable. Moreover, cutoff scores for identifying children with mismatched explicit and applied theory of mind were proposed to determine the priority of interventions.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, [gamma]-Amino-n-butyric acid, glutamine, sarcosine, [delta]-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism.

A new safety assessment framework has been proposed to address the operational risks of the integration of wind power and photovoltaic grid, which integrates the characteristics of distributed power sources with the dynamic reconfiguration requirements of the distribution grid. The framework comprehensively considers the impacts of wind power and photovoltaic output uncertainties, as well as load fluctuations, on the stability of the distribution grid. It also evaluates the safety under different operational states of the distribution grid. Using Halton sequence sampling technology to accurately simulate the output of distributed power sources and the status of system components, combined with CPLEX optimisation for solving, a dynamic reconfiguration model is constructed to address potential faults in the distribution grid. Introducing the combined weighting method, a comprehensive risk assessment system for voltage violations, power flow violations, and load shedding has been constructed. The effectiveness of this method has been validated through simulations on the IEEE33 bus and IEEE118 bus systems, providing new insights to improve the safety and reliability of distribution grids.

Abstract Land use and cover change (LUCC) significantly impacts global carbon cycles and land surface properties, accounting for 25% of the historical atmospheric CO2 increase. We explore a previously overlooked role of LUCC in driving the land carbon cycle by using a three-level meta-analysis and Land Use Harmonization data to drive an ecosystem model. Our findings reveal that a loss of 39.2% of soil organic carbon (SOC) change in China due to LUCC, mitigated by afforestation, doubles gross primary productivity at 0.02 Pg C yr−1, countering central China’s urbanization decline. Indirect climate effects, especially soil bulk density, significantly impact SOC compared to direct climate effects. LUCC has significantly increased the Chinese terrestrial carbon sink, with net ecosystem productivity reaching 0.02 ± 0.12 Pg C yr−1. Our study underscores the importance of reforestation and afforestation in addressing climate change and enhancing carbon sinks in future carbon management.

Abstract Background Brominated flame retardants (BFRs) are widely utilized to mitigate the flammability of various materials. Previous studies have revealed the impact of BFRs exposure on hormonal disruption and bone metabolism which are closely related to periodontitis. However, it remains unknown the potential relationship between BFRs and periodontitis. This study aimed to explore the association between BFRs exposure and periodontitis in US adults. Methods The data analyzed in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009–2014. Twelve serum BFRs were quantified using isotope dilution gas chromatography high-resolution mass spectrometry. Univariable and multivariable logistic regression was employed to evaluate the association between serum BFRs and periodontitis. Bayesian kernel machine regression (BKMR) analyses were utilized to assess the association between mixtures of BFRs and periodontitis. Results A total of 3311 eligible participants were included. Serum BFRs (PBDE-47, PBDE-99, and PBDE-154) were significantly associated with periodontitis, and the odds ratios (ORs) and corresponding 95% confidence intervals(CIs) were 1.15(1.01,1.29), 1.10(1.01,1.20), and 1.12(1.01,1.25), respectively. Notably, these three BFRs were also significantly associated with the severity of periodontitis. Additionally, the BKMR model revealed a significant association between the mixture of all twelve BFRs and periodontitis. Conclusions This preliminary study suggests a significant association between specific serum BFRs (PBDE-47, PBDE-99, and PBDE-154) and periodontitis and its severity. Further prospective and experimental studies are warranted to validate our findings.

Abstract Background As a currently incurable but preventable disease, the prevention and early diagnosis of Alzheimer’s disease (AD) has long been a research hotspot. Amyloid deposition has been shown to be a major pathological feature of AD. Notably, not all the people with amyloid-beta (Aβ) pathology will have significant cognitive declines and eventually develop AD. Therefore, the aim of this study was to explore the risk factors for cognitive decline in Aβ-positive participants. Methods We included 650 non-demented participants who were Aβ-positive at baseline from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Mixed effects and COX regression models were applied to assess 37 potential risk factors. Mixed effects models were employed to assess the temporal associations between potential risk factors and four cognitive assessment scales. COX regression models were used to assess the impact of potential risk factors on cognitive diagnosis conversion. Univariate and multivariate analyses were applied to the above models. Additionally, we used the Cochran-Armitage trend test to examine whether the incidence of cognitive decline increased with the number concurrent of risk factors. Results Six factors (low diastolic pressure, low body mass index, retired status, a history of drug abuse, Parkinsonism, and depression) were the identified risk factors and four factors (a history of urinary disease, musculoskeletal diseases, no major surgical history, and no prior dermatologic-connective tissue diseases) were found to be suggestive risk factors. The incidence of cognitive decline in the Aβ-positive participants gradually increased as the number of concurrent risk factors increased (p for trend = 0.0005). Conclusions Our study may facilitate the understanding of the potential pathological processes in AD and provide novel targets for the prevention of cognitive decline among participants with Aβ positivity.

Abstract Background Transposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates. Methods A total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals. Results The population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO. Conclusion Earlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a serious threat to global public health. Fluoroquinolones (FQs) are effective against M. tuberculosis; however, resistant strains have limited their efficacy. M ycobacterium fluoroquinolone resistance protein A (MfpA) confers intrinsic resistance to FQs; however, its regulatory mechanisms remain largely unknown. Using M. smegmatis as a model, we investigated whether MfpC is necessary for FQ susceptibility. MfpC mutants were sensitive to moxifloxacin, indicating that MfpC is involved in FQ susceptibility. By testing the mfpC inactivation phenotype in different mutants and using mycobacterial protein fragment complementation, we demonstrated that the function of MfpC depends on its interactions with MfpB. Guanine nucleotide exchange assays and site-directed mutagenesis confirmed that MfpC acts as a guanine nucleotide exchange factor to regulate MfpB. We propose that MfpB influences MfpA at the translational level. In summary, we reveal the role of MfpC in regulating the function of MfpA in FQ resistance.

Abstract Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP–SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP–SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP–SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP–SNP interaction detection accuracy.

Abstract Background Microglial activation has been suggested to be involved in the pathogenesis of depression and Alzheimer’s disease (AD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a marker of microglial activation. The purpose of this study was to investigate the interrelationships of cerebrospinal fluid (CSF) sTREM2, AD pathology, as well as minimal depressive symptoms (MDSs), and cognition. Methods A total of 545 non-demented individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort were included in our study. The average age of the total population was 72.6 years and the percentage of females was 42.6%. Linear regression models were conducted to investigate the linear relationships of MDSs with CSF sTREM2, AD pathology, cognition, and brain structure. Mediation models and structural equation models (SEM) were conducted to examine whether CSF sTREM2 mediated the relationships of MDSs with AD pathology and cognition. Results Results revealed that individuals with MDSs had lower CSF sTREM2 levels than normal controls. Linear regression showed that MDSs were linearly associated with CSF sTREM2 (P FDR = 0.012) and amyloid biomarkers (P FDR < 0.05), as well as cognitive scores (P FDR < 0.05) and hippocampal volume (P FDR = 0.003). Mediation analyses revealed that CSF sTREM2 mediated the association between MDSs and amyloid pathology, with the mediating proportions ranging from 6.030 to 18.894%. However, SEM failed to reveal that MDS affected cognition through CSF amyloid pathology and CSF sTREM2. Conclusions MDSs are associated with amyloid pathology and cognition. CSF sTREM2 may potentially be an intervenable target between depression and AD pathology.

Abstract Background Hepatocellular carcinoma (HCC) constitutes an important contributor to fatalities. Coronavirus disease 2019 (COVID-19) frequently presents with complications such as respiratory distress, systemic inflammatory responses, and damage to various organs. Several studies have investigated the relationship between COVID-19 and mortality in patients with liver cancer, but there are few research on the relationship between them. This study is to explore the correlation between the two diseases and drugs treating them. Methods The Gene Expression Omnibus (GEO) database provides gene datasets of COVID-19 patients and HCC patients. Through differential gene analysis and weighted gene co-expression network analysis, we determined 223 genes represented in HCC and COVID-19. We then used functional annotation, protein–protein interaction network construction, predictive model development and verification, prognostic value analysis, and miRNA–gene network construction. Besides, we created a drug–hub–gene network by predicting possible medications that interact with hub genes using the Drug–Gene Interaction Database (DGIdb). Ultimately, we applied immunohistochemistry to ascertain the hub genes expression. Results This study revealed that eight core genes (RRM2, TPX2, DTL, CDT1, TYMS, CDCA5, CDC25C, and HJURP) co-existed in both HCC and COVID-19 and were differentially expressed in both HCC and normal tissues.CDC25C, RRM2, CDCA5, and HJURP had diagnostic value (AUC > 0.8) and prognostic value (adjusted P-value

Abstract Background A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. Methods Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. Results Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. Conclusions The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease.

Background/purpose: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. Methods: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. Results: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2–10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). Conclusion: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Abstract Understanding protein function is pivotal in comprehending the intricate mechanisms that underlie many crucial biological activities, with far-reaching implications in the fields of medicine, biotechnology, and drug development. However, more than 200 million proteins remain uncharacterized, and computational efforts heavily rely on protein structural information to predict annotations of varying quality. Here, we present a method that utilizes statistics-informed graph networks to predict protein functions solely from its sequence. Our method inherently characterizes evolutionary signatures, allowing for a quantitative assessment of the significance of residues that carry out specific functions. PhiGnet not only demonstrates superior performance compared to alternative approaches but also narrows the sequence-function gap, even in the absence of structural information. Our findings indicate that applying deep learning to evolutionary data can highlight functional sites at the residue level, providing valuable support for interpreting both existing properties and new functionalities of proteins in research and biomedicine.